This project focuses on basic and applied research on human retroviruses, HIV-1 and HTLV-I. It covers three broad areas: I) basic research studying the regulated expression of HIV-1; II) basic research on cellular transformation events as related to HTLV-I; and III) applied research towards developing HIV-1-based vectors and designing molecular ribozymes targeted against HIV-1. Some notable scientific findings from our research program in 2000-2001 include: 1) the definition of ATM as a factor in HTLV-I repression of p53 function; 2) the elucidation of cyclin A as a cellular factor in HTLV-I-directed cell cycle progression; 3) the definition of genes that are up- and down- regulated by HTLV-I Tax oncoprotein using chip array technology; 4) the development of a constitutively-dead, conditionally-live HIV-1 attenuated genome; 5) the development of aromatic polyamidines as a Tat-TAR inhibitor.